With her enormous eyes, long limbs, and a melodic voice that sounds like it’s asking a question even when it isn’t, Judy Greer was built for ’30s screwball comedies, But bit by bit, Greer has tried on just about every character role imaginable: as a nerd (Jawbreaker), a mean girl (also Jawbreaker), a suicidal file clerk (What Women Want), a nervous assistant (The Wedding Planner), a literary muse (Adaptation.), and a member of the Jewish Justice League (The Hebrew Hammer). In just 12 years, she’s done approximately 80 projects in TV and film.

Up until now, Greer has most often been recognized for her outrageous turn as Arrested Development’s Kitty Sanchez, the ditsy secretary given to flashing her boobs and announcing, “Say goodbye to these!” But with a fistful of new projects, it’s obvious that, for Greer, playing Kitty was just a warm-up. Lately, you’ve probably seen her in Two and a Half Men 2.0 as Bridget, the ex-wife who has ruined Ashton Kutcher’s billionaire Walden for all other women. “I was driving by a café on Melrose when I found out I was going to be on Two and a Half Men,” says Greer. “I was like, You’re swear-word kidding me.” After a pause, she clarifies: “I said the F-word.” Greer is also getting some buzz with a dramatic role in Alexander Payne’s much-anticipated bittersweet movie The Descendants, which opens November 18. Considering that Greer learned her craft at DePaul University’s prestigious Theatre School, can Chicago take credit for her success? “You may,” says Greer graciously.

Behind the Scenes: Judy Greer Cover Shoot

Greer grew up outside Detroit, but she spent close to five years in Chicago in the ’90s. “I remember that up until right about now, that was the happiest time of my life,” says Greer. One of her favorite things was to walk on Michigan Avenue late at night after all the stores had closed. “I used to love to go window shopping because I was too broke to buy anything,” she says. “I like that, the memory of nighttime Chicago. In the summer, it’s so magical. It’s so hot out, you feel like [you] could walk around all night long in a sundress with a credit card in [your] pocket.”

DePaul University is where Greer learned to be fearless. “You have to do some really weird things in acting school,” she says. “At the time you’re like, I’m never actually going to have to play the role of a tiger. But not too long ago, I got a part where I had to be a jerk in front of a bunch of people, and I thought, Oh! Maybe that’s what that was about. Being comfortable making an ass of myself—I think that’s what a lot of acting school is.”

TOP: Greer as the nervous assistant to boss Jennifer Lopez in The Wedding Planner. BOTTOM: Greer as Jennifer Garner’s sarcastic frenemy in 13 Going on 30.

Finding Her Footing
Greer nabbed her first professional acting credit on the series Early Edition. “That was sort of like the Law & Order of Chicago—all the local actors got to be in it,” she says. Greer played a macrobiotic pastry chef, but it was costar Fisher Stevens’s cell phone—before they became ubiquitous—that made more of an impact on her. “I’d never seen one before! I thought, He must be rich!” she says. “Isn’t that sad? I can’t remember the birthdays of my loved ones, but I have such a vivid memory of Fisher Stevens’s phone.”

During school she worked as a waitress, a telemarketer, and, for a single day, as an oyster shucker. “It’s so flippin’ hard to shuck an oyster,” she says. It was just a couple of years later that Greer found herself shooting a love scene with George Clooney in 1999’s Three Kings. She played a news correspondent trying to get a story out of Clooney’s character. “That was a fun day,” says Greer. “I remember shooting that. We had to do so many takes of the scene that I was like, Are they playing a joke on me?”

In The Descendants, Greer costars with Clooney again. He plays a wealthy landowner in Hawaii who’s struggling to take care of his daughters while his wife is in a coma. His feelings are further complicated when he learns that his wife had been cheating on him; Greer plays the wife of the guy she was cheating with. She was eager to work with director Alexander Payne (Sideways, Election), she says. And he returned the compliment with a juicy scene near the end of the film that teeters between comedy and tragedy—Greer’s character veers from polite to awkward to sad to angry to defensive. Somehow, on top of it all, she’s funny. It’s the stuff Oscars are made of.

“The movie is just so moving,” says Greer. “I’ve only seen it once so far, and all the people in the audience were crying—and they were agents! It’s not the kind of movie you just leave and say, ‘Where do you want to eat?’ You’re like, ‘No, I need to think about this.’” She’s also into her third season of FX’s raunchy spy cartoon Archer. Greer voices Cheryl, the kind of woman who thinks you can take a pregnancy test online. “It’s the perfect job, it really is,” says Greer. “Yesterday’s workday was 20 minutes long.”

The Acting Life
Still, all the traveling and intensity of life as an actor takes its toll, which is why Greer agreed to star in the Yahoo! Web series Reluctantly Healthy, in which a health and fitness dream team try to teach her how to take care of herself on the go. “I’m learning how unhealthy I am,” laughs Greer. “And I’m learning how hard it is not to act, but to be yourself in something. It’s so weird and out of my comfort zone. You’re always supposed to do stuff you’re afraid of, and I’m afraid of this.”

Another role that doesn’t come easy to Greer: glamorous diva. “I always feel like I’m playing dress up in crazy fancy outfits,” she says. “This is a business of [how] you look, but I’m most comfortable playing characters. It’s when I have to play myself that I have the most problems. I’m like, I don’t know what to do! So I might say to myself, Tonight you’re going to be Elizabeth Hurley on the red carpet.” But Greer has another incentive to look good: In December, she’ll marry boyfriend Dean Johnsen, whom she met almost a year and a half ago on a blind date. He produces HBO’s Real Time with Bill Maher. Unlike most celebrity spouses, “He’s like a normal human man,” says Greer.

At the start of 2011, Greer sat down to make lists of her goals. “Now I’m starting to think more along the lines of, Whom do I want to work with?” she says. “I don’t think, Oh, I want to do TV or I want to do movies, but [rather] which projects can I weasel my way into and get the most experience possible?”

She can already check many of her favorite directors off her list: David O. Russell, M. Night Shyamalan, and Cameron Crowe, to name three. Crowe, in fact, recommended her to another director by saying, “She’s so good and effortless. Do yourself a favor and work with her.”

“I have fun working, no matter what,” says Greer. “I always try to fall in love with my characters.” Which is probably why the audience falls in love with them, too.

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